Device for monitoring a patient for a urinary tract infection

ABSTRACT

The invention provides for a urinary monitoring device to monitor for the presence or absence of markers indicative of a urinary tract infection (UTI). The invention also provides for methods of using such a device.

TECHNICAL FIELD

This invention relates to medical devices, and more particularly to adevice for monitoring a patient for a urinary tract infection.

BACKGROUND

Urinary tract infections are a major cause of morbidity and mortality inhealthcare, especially in hospitalized and otherwise debilitatedpatients. Catheter-associated UTI (CAUTI) is the most common nosocomialinfection, accounting for more than 40% of all hospital-acquiredinfection. The risk of infection is substantially increased in patientshaving a urinary catheter. In addition, many afflicted patients areunable to verbalize their symptoms and their infections may not berecognized until they are in advanced stages such as life-threateningsepsis.

CAUTI is the second most common cause of nosocomial sepsis afterpneumonia. More than 750,000 patients in the United States developsevere sepsis each year, which is characterized by acute organ systemdysfunction. The mortality rate from severe sepsis, at 28.6%, leaves215,000 Americans dead annually at an estimated cost of about $16.7billion. This is nearly 600 patients per day, which means that as manypatients in the United States die from severe sepsis each day as diefrom acute myocardial infarction.

Obviously, it is desirable to discover catheter-associated UTI's asearly as possible. Urine “dipsticks” are available (e.g., Multistix®,Bayer, Leverkusen, Germany; Chemistrip®, Roche Diagnostics,Indianapolis, Ind.; Multistix® 10 SG, Miles Laboratories, Inc., Elkhart,Ind.; and Combur-Test®, Boehringer Mannheim Corp., Indianapolis, Ind.),but require an index of suspicion, are labor-intensive for nursingstaff, and usually require incident-specific physician orders. Morecommonly, urine specimens are sent to a hospital or central laboratorywhen certain indicators such as cloudiness, a change in color, and/orblood are observed.

Current procedures can result in a significant lapse of time before theUTI is clinically diagnosed and treatment initiated. Ultimately, thecost of these infections in both dollars and human life is substantial.The present disclosure provides systems and devices that monitor apatient for a UTI as well as methods of using such systems and devices.Using the disclosed systems and devices, particularly on catheterizedpatients, can significantly reduce or completely eliminate the currentdelays in diagnosis and treatment of UTIs.

SUMMARY

In one aspect, the invention provides a urinary tract infection(UTI)-monitoring urinary catheter system for monitoring the presence orabsence of one or more markers in urine that are indicative of a urinarytract infection (UTI). Such a UTI-monitoring system generally includes acatheter portion, a collection tubing portion, and a collection bagportion. At least one of those portions includes a UTI indicatorsubstrate that detects and signals the presence or absence of the one ormore markers in urine that are indicative of a UTI. In certainembodiments, the catheter portion contains the UTI indicator substrate;in certain embodiments, the collection tubing portion contains the UTIindicator substrate; and in certain embodiments, the collection bagportion contains the UTI indicator substrate.

In another aspect, the invention provides a UTI monitoring device formonitoring the presence or absence of one or more markers in urine thatare indicative of a urinary tract infection (UTI). Such a UTI-monitoringdevice can be configured for placement in-line in a urinary cathetersystem. Such a UTI-monitoring device generally includes a tubularportion that has a first port on one end and a second port on the otherend that are configured for in-line placement at a position along aurinary catheter system. The tubular portion of such a device alsoincludes a UTI indicator substrate for detecting and signaling thepresence or absence of the one or more markers in urine that areindicative of a UTI.

The UTI indicator substrate can be attached (e.g., releasably attached)to an inside surface of the at least one portion of the UTI-monitoringsystem or device. In some embodiments, a UTI-monitoring system or devicecontains more than one UTI indicator substrate. Representative markersin urine that are indicative of a UTI include leukocyte esterase and/ornitrites. A UTI indicator substrate can include at least one detectorcomponent and at least one signal component. Representative detectorcomponents include an antibody that has specific binding affinity forthe one or more markers in urine that are indicative of a UTI, andrepresentative signal components include a colorimetric change and adigital read-out.

In still another aspect, the invention provides methods of monitoring acatheterized patient's urine for the presence or absence of one or moremarkers indicative of a UTI. Such a method comprises catheterizing thepatient with the UTI-monitoring urinary catheter system as describedherein or placing a UTI-monitoring device as described herein in aurinary catheter system, and monitoring the patient's urine for thepresence or absence of one or more markers indicative of a UTI.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present invention, suitable methods andmaterials are described below. In addition, the materials, methods, andexamples are illustrative only and not intended to be limiting. Allpublications, patent applications, patents, and other referencesmentioned herein are incorporated by reference in their entirety. Incase of conflict, the present specification, including definitions, willcontrol.

The details of one or more embodiments of the invention are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the invention will be apparent from thedrawings and detailed description, and from the claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is a schematic of one embodiment of a UTI-monitoring urinarycatheter system in which the UTI indicator substrate is attached to theinside wall of the collection bag portion.

FIG. 2 is a schematic showing one embodiment of a UTI-monitoring devicethat can be positioned in-line in a urinary catheter system.

FIG. 3 is a schematic showing an embodiment of a UTI-monitoring devicehaving multiple UTI indicator substrates contained within a dialing- orratcheting-type mechanism.

FIG. 4 is a representative example of standing orders that a physiciancan use when a UTI-monitoring system or device is employed.

Like reference symbols in the various drawings indicate like elements.

DETAILED DESCRIPTION

Urinary tract infection (UTI)-monitoring systems and devices aredisclosed herein. The systems and devices disclosed herein providetimely, sensitive, and specific information regarding the presence orabsence of markers in urine that are indicative of a UTI. The systemsand devices disclosed herein provide timely information regarding UTIs,which is specifically valuable in patients who have a urinary cathetersystem in place. Urinary catheter systems are well known in the art, andgenerally include a catheter portion, a collection tubing portion, and acollection bag portion. See, for example, U.S. Pat. Nos. 4,575,371;4,579,554; 4,813,935; 4,936,837; 5,295,979; 5,300,051; 5,785,694;5,919,170; 6,117,120; 6,162,201; and 6,837,868.

This disclosure describes a UTI-monitoring urinary catheter system,which is useful for monitoring the presence or absence of one or moremarkers in urine that are indicative of a urinary tract infection (UTI).A UTI-monitoring urinary catheter system typically includes a catheterportion, a collection tubing portion, and a collection bag portion. Atleast one of those portions, in a UTI-monitoring urinary cathetersystem, contains a UTI indicator substrate. A UTI indicator substratedetects and signals to a user whether or not one or more markers arepresent in the urine that are indicative of a UTI.

FIG. 1 shows one representative example of a UTI-monitoring urinarycatheter system. The UTI-monitoring urinary catheter system shown inFIG. 1 includes a conventional Foley catheter system having a urinarycatheter C portion, a collection tubing T portion, and a collection bagB portion. A drainage outlet O also is shown on collection bag B. In theembodiment shown in FIG. 1, a UTI indicator substrate 40 is attached tothe inside surface of the collection bag B. A UTI indicator substrate 40can be attached to the inside surface of any portion of a urinarycatheter system, however, provided that the UTI indicator substrate 40comes into contact, at least momentarily, with the urine moving throughthe urinary catheter system. One or more UTI indicator substrates can beplaced within one or more portions of the urinary catheter systemduring, for example, the manufacturing process.

In some embodiments, one or more portions of a urinary catheter system(e.g., the catheter portion, the collection tubing portion, or thecollection bag portion) can contain a receptacle or the like into whicha UTI indicator substrate can be placed. It is envisioned thatreceptacles or the like can be designed in a urinary catheter systemthat allow for removing one (e.g., used) indicator substrate andreplacing it with another (e.g., fresh) indicator substrate. Such areceptacle or the like must allow for the UTI indicator substrate tocontact the urine, however, it is understood by those in the art thatthe use of any type of releasable, removable, or replaceable UTIindicator substrate must not jeopardize the sterility and integrity ofthe closed urinary catheter system.

This disclosure also describes a UTI-monitoring device. Similarly to aUTI-monitoring urinary catheter system, a UTI-monitoring device isuseful for monitoring the presence or absence of one or more markers inurine that are indicative of a UTI. A UTI-monitoring device can be adevice that is configured, for example, for in-line placement in aconventional urinary catheter system. For example, a UTI-monitoringdevice can be configured to be placed in-line within a catheter portion,a collection tubing portion, or a collection bag portion, or as anin-line fitting for placement between a catheter portion and acollection tubing portion or between a collection tubing portion and acollection bag portion. As with the removal or replacement of a UTIindicator substrate in a UTI-monitoring urinary catheter system, theplacement or replacement of a UTI-monitoring device (e.g., in-line) by auser must not jeopardize the sterility and integrity of the closedsystem.

FIG. 2 shows a UTI-monitoring device for in-line placement. An in-lineUTI-monitoring device generally has a tubular portion 10 through whichurine flows. The UTI-monitoring device shown in FIG. 2 has a UTIindicator substrate 40 attached to the inside wall of the tubularportion 10 positioned in such a way that the UTI substrate indicator 40comes into contact with the urine. The tubular portion 10 of an in-lineUTI-monitoring device generally has an appropriately sized first port 20on one end and an appropriately sized second port 30 on the other endfor in-line placement in a urinary catheter system. In the embodimentshown in FIG. 2, the signal 44 is visible through a window 12 in thetubular chamber 10. The signal in FIG. 2 is shown as a ‘plus’ sign,which indicates, for example, a positive result (i.e., the presence of aUTI marker in the urine).

A UTI-monitoring device can be manufactured in individual units that areplaced in-line in a urinary catheter system by a user (e.g., a nurse,attendant, or caretaker). Alternatively, a UTI-monitoring device can bemanufactured as an integral part of one or more of the portions of aurinary catheter system. A UTI-monitoring device also can have featuressuch as an anti-reflux valve to minimize or eliminate any backflow ofurine. Although a UTI-monitoring device is disclosed herein that isconfigured for in-line placement, a UTI-monitoring device can have anynumber of configurations provided that the UTI indicator substrate or acomponent thereof contacts the urine traveling through or collected in aurinary catheter system.

As an alternative to a UTI indicator substrate being attached to theinside wall of a portion of a UTI-monitoring system or a UTI-monitoringdevice, a UTI indicator substrate 40 can be configured forcross-sectional placement within the system or device. A cross-sectionalconfiguration of a UTI indicator substrate brings the urine into contactwith the UTI indicator substrate without impairing the flow of urinethrough the urinary drainage system. In such a cross-sectionalembodiment, a signal indicating the presence or absence of a markerindicative of a UTI can be visualized, for example, by a colorimetricchange in all or a portion of the UTI indicator substrate.

A UTI indicator substrate for use in either a UTI-monitoring system or aUTI-monitoring device generally includes a detector component and asignal component. The detector component detects the presence or absenceof one or more markers that are indicative of a UTI, and the signalcomponent provides an indication, usually visual, of the presence orabsence of one or more of such markers. Depending upon the particularinteraction between the components, the detector component and thesignal component can be together as (or on) a single moiety, or thecomponents can be two (or more) moieties. Two (or more) moieties may beseparated (e.g., spatially), or may co-exist at essentially the sameposition on the indicator substrate. In some instances, two (or more)moieties may be physically attached to one another, for example, withcovalent bonds. In some instances, the detector component and the signalcomponent of a UTI indicator substrate can be placed directly on a wallof a portion of the system or of a device without the presence of anactual ‘substrate.’

Detector and signal components are used routinely in the art oflaboratory testing and diagnostics. For example, dip-stick tests, homepregnancy tests, tests for strep throat (e.g., Rapid Strep Test®),glucose meters, and tuberculosis DFA tests all utilize some form ofdetector and signal components. See, for example, Vaitukaitis et al.,1972, Am. J Obst. Gynecol., 113:751-8; and U.S. Pat. Nos. 5,602,040;5,622,871; 5,656,503; and 5,712,172 and references cited therein. AUTIindicator substrate can be configured in a number of different waysincluding a reagent strip, a coated bead, or other suitable means usedin the art. A UTI indicator substrate can be made of durable material(s)that can maintain the integrity of the detector and signal componentsfollowing exposure to urine for an extended period of time, or the UTIindicator substrate can be periodically changed and scored immediatelyor shortly after exposure to urine.

As described herein, a UTI indicator substrate detects one or moremarkers in urine that are indicative of a UTI. Detector components areknown in the art. Representative detector components include, withoutlimitation, antibodies (for antigen-specific binding) or antigens (forantibody-specific binding). Immunoassays and enzymatic assays areroutine in the art, and numerous methods are known in the art fordetecting markers in body fluids such as urine. See, for example,Current Protocols in Immunology, 1997, Coligan et al., Eds., John Wiley& Sons, Inc., NY; Current Protocols in Molecular Biology, 1997, Ausubelet al., Eds., John Wiley & Sons, Inc., NY; and U.S. Pat. Nos. 3,438,737;3,359,072; 3,418,079; and 4,013,416.

A marker found in urine that is indicative of a UTI is leukocyteesterase, also known as white blood cell (WBC) esterase. The presence ofleukocyte esterase in urine is an indication that white blood cells arepresent, which indicates infection of one or more structures of theurinary tract. See, for example, Simerville et al., 2005, Am. Fam.Physician, 71:1153-62; Young et al., 2001, Infect. Dis. Obstet.Gynecol., 9:249-55. Czerwinski et al., 1971, Amer. J. Obstet. Gynec.,10:677; Notelovitz et al., 1970, S. A. Med. J, 44:1128; and Beer et al.,1996, Brit. Med. J, 313:25; and U.S. Pat. Nos. 4,278,763; 4,331,760;4,469,789; 4,551,428; 4,637,979; 4,645,842; 4,657,855; 4,704,460;4,758,508; 5,512,450; 5,663,044; 5,776,780; 6,013,465; and 6,855,491. Inaddition to or as an alternative to detecting leukocyte esterase, thelevel of nitrites in the urine can be used to monitor a patient for aUTI. Nitrites are typically present in a patient developing or having aUTI because many species of bacteria that colonize the urine and urinarytract convert nitrates derived from dietary metabolites into nitrites.See, for example, Fuchs & Gutensohn, 1967, Dtsch. Med. J., 10:343; andU.S. Pat. Nos. 4,434,235; 5,759,860; and 5,776,715.

Representative signal components include, without limitation, a chemicalreaction, a colorimetric reaction, a photochemical reaction,fluorescence, or the like. The result of the signal component (i.e., theindication of the presence or absence of one or more compoundsindicative of a UTI) and can be, for example, visible to the user. Asignal can be in the form of a color change (e.g., red in the presenceof a marker indicative of a UTI and white in the absence of the marker),a symbol (e.g., “+” or “−”), words (e.g., “yes” or “no”), or anycombination thereof to signify the presence or absence of one or moremarkers in the urine indicative of a UTI. In yet another embodiment, adetector component can be coupled to a light or other electronic signalat the bedside, the nursing station, or remotely via wireless means.

In some embodiments, a UTI-monitoring system or device can be configuredto contain multiple UTI indicator substrates. FIG. 3 shows an embodimentof a single use in-line UTI-monitoring device containing multiple UTIindicator substrates for use over a period of time. The device shown inFIG. 3 contains a rotary-type dial or a ratcheting-type knob 14 or othersimilar mechanism that, when employed, exposes a fresh UTI indicatorsubstrate (e.g., a fresh detector component) to the urine flow. Thedialing or ratcheting movement may break a seal, peel away a protectivelayer, open a blister-pack, or move, for example, a detector componentfrom a closed or sealed portion of the device into contact with theurine. Although the dialing- or ratcheting-type embodiment shown in FIG.3 is configured for in-line placement in a urinary catheter system, adialing- or ratcheting-type embodiment is not limited to such a design.For example, a UTI-monitoring system or device can be designed toreceive a cartridge or cassette or the like containing multiple UTIindicator substrates. A dialing- or ratcheting-type of UTI-monitoringdevice having multiple UTI indicator substrates or a cartridge orcassette or the like also can have a numerical indicator 16 to trackusage.

In addition to monitoring the presence or absence of markers in urinethat are indicative of a UTI, a UTI-monitoring urinary catheter systemor a UTI-monitoring device can be configured to monitor other markers,compounds, reagents, drugs, metabolites, or other characteristics orqualities of the urine. For example, specific gravity, pH, protein,glucose, ketones, bile, hemoglobin (blood), urobilinogen, sodium,potassium, or any combination thereof can be monitored in the urine. Inaddition, a UTI indicator substrate as described herein can beconfigured to monitor, for example, a substance (e.g., a drug) todetermine or maintain, for example, a threshold level (e.g., maximaltherapeutic value without toxicity) using methods routine in the art.

In clinical use, a UTI indicator substrate associated with either aUTI-monitoring urinary catheter system or a UTI-monitoring device can bereadily scored, for example, at each periodic check of the patient'svital signs. In an embodiment in which a UTI-monitoring device or systemcontains multiple UTI-indicator substrates (e.g., a dialing- orratcheting-type embodiment), the dial or knob can be rotated to expose anew UTI indicator substrate to the urine and immediately scored by thenurse or attendant checking vital signs. When a positive signal isnoted, the patient's physician can be contacted for further orders or apredetermined protocol can be activated based on the patient's clinicalscenario and medical history. FIG. 4 shows representative standingorders that might be used by a physician when a UTI-monitoring system ordevice as described herein is employed. For example, an appropriateantibiotic regimen can be initiated while awaiting formal laboratoryresults on the patient's urine.

The use of a UTI-monitoring system or device such as that disclosedherein can detect a UTI or a potential UTI very early in its course andallow for prompt treatment. The UTI-monitoring systems and devicesdescribed herein can significantly reduce the risks associated withindwelling urinary catheters and improve the standard of care for suchpatients. The UTI-monitoring systems and devices described herein are ofparticular value to patients that are at high risk of developing a UTI(e.g., patients requiring a long-term urinary catheter) such as headinjury patients, patients having a broken spinal cord or a brokenpelvis, or comatose patients and may be the difference between life anddeath for an immunocompromised high-risk patient such as a burn patient.The UTI-monitoring systems and devices, however, can be used by anycatheterized patient (e.g., a woman in labor, or a patient undergoingoutpatient surgery).

The UTI-monitoring systems and devices described herein can result in asignificant decrease in the morbidity and mortality ofcatheter-associated UTIs, which are usually very responsive to treatmentonce identified. Use of a UTI-monitoring system or device also canresult in substantial financial savings by cost-effectively treatingUTIs at an early stage, thereby preventing the progression to more lifethreatening and costly systemic infections.

OTHER EMBODIMENTS

It is to be understood that while the invention has been described inconjunction with the detailed description thereof, the foregoingdescription is intended to illustrate and not limit the scope of theinvention, which is defined by the scope of the appended claims. Otheraspects, advantages, and modifications are within the scope of thefollowing claims.

1. A urinary tract infection (UTI)-monitoring urinary catheter systemfor monitoring the presence or absence of one or more markers in urinethat are indicative of a urinary tract infection (UTI) comprising acatheter portion, a collection tubing portion, and a collection bagportion, wherein said collection tubing portion further comprisesmultiple UTI indicator substrates, wherein said multiple UTI indicatorsubstrates are configured to be serially exposed to multiple freshlyvoided urine specimens along said collection tubing portion, whereinsaid multiple UTI indicator substrates are sequestered from one anotherand from the urine but, when exposed to a freshly voided urine specimen,are capable of detecting and signaling the presence or absence of one ormore markers in said freshly voided urine specimen that are indicativeof a UTI.
 2. The UTI-monitoring urinary catheter system of claim 1,wherein said UTI indicator substrate is separately and sequentiallyexposed to urine inside of said collection tubing portion.
 3. TheUTI-monitoring urinary catheter system of claim 1, wherein said multipleUTI indicator substrates are releasably attached to an inside surface ofsaid collection tubing portion.
 4. The UTI-monitoring urinary cathetersystem of claim 1, wherein each of said multiple UTI indicatorsubstrates detects leukocyte esterase.
 5. The UTI-monitoring urinarycatheter system of claim 4, wherein each of said multiple UTI indicatorsubstrates further detects nitrites.
 6. The UTI-monitoring urinarycatheter system of claim 1, wherein at least one of said multiple UTIindicator substrates detects nitrites.
 7. The UTI-monitoring urinarycatheter system of claim 1, wherein the UTI indicator substratecomprises an antibody that has a specific binding affinity for said oneor more markers in urine that are indicative of a UTI.
 8. TheUTI-monitoring urinary catheter system of claim 1, wherein the presenceof one or more markers in said freshly voided urine is indicated by acolorimetric change.
 9. A UTI monitoring device for monitoring thepresence or absence of one or more markers in urine that are indicativeof a urinary tract infection comprising a first port on one end and asecond port on the other end, wherein said first and second ports areconfigured for in-line placement within a collection tubing portion of aurinary catheter, wherein, located between said first and second portsare multiple UTI indicator substrates, wherein said multiple UTIindicator substrates are configured to be serially exposed to multiplefreshly voided urine specimens, wherein said multiple UTI indicatorsubstrates are sequestered from one another and from the urine but, whenexposed to a freshly voided urine specimen, can detect and signal thepresence or absence of said one or more markers in said freshly voidedurine specimen that are indicative of a UTI.
 10. A method for monitoringa catheterized patient's urine for the presence or absence of one ormore markers indicative of a UTI comprising catheterizing a patient witha urinary catheter system comprising multiple UTI indicator substrates,wherein said multiple UTI indicator substrates are configured to beserially exposed to multiple freshly voided urine specimens along acollection tubing portion, wherein said multiple UTI indicatorsubstrates are sequestered from one another and from the urine but, whenexposed to a freshly voided urine specimen, are capable of detecting andsignaling the presence or absence of one or more markers in said freshlyvoided urine specimen that are indicative of a UTI, exposing at leastone of said UTI indicator substrates to a freshly voided urine specimen,and monitoring said exposed UTI indicator substrate to observe whetherit signals the presence or absence of said one or more markersindicative of a UTI.